By borrowing a system found in plants, researchers can turn off sperm production in an inducible, reversible, and non-toxic manner
Let’s say you want to study how your favorite gene affects aging. You pick Caenorhabditis elegans for your study because it is one of the most important models of aging, and you put some of the worms on a plate—but within days, they multiply, and suddenly your plate is a random mix of worms young and old! How are you supposed to study how long these nematodes live? A new system reported in G3: Genes|Genomes|Genetics provides a handy solution: a reversible way to sterilize your worms at the start of the experiment.
Kasimatis et al. set out to create a system for inducing sterility in C. elegans so that mating can be precisely controlled in the lab—whether for aging experiments or for studies in which controlling the timing of mating is beneficial, such as investigations of sexual reproduction itself. While methods like treatment with the chemotherapy agent FUdR have been used for some time, these systems are typically toxic and have off-target effects.
To create a method that was inducible, non-toxic, and reversible, the authors used the auxin-induced degradation (AID) system, which originates from Arabidopsis thaliana. In plants, the hormone auxin causes TIR1 to mark other proteins for ubiquitin-mediated degradation by adding a degron tag. The authors generated worms that express plant TIR1 and have degron tags on the gene spe-44, which is crucial for production of sperm. In these worms, auxin treatment leads TIR1 to degrade spe-44, thus preventing the worms from making sperm.
C. elegans has two sexes: hermaphrodite and male, and the authors tested the AID system in both. Auxin treatment in their model induced self-sterility in both hermaphroditic and male worms, just as expected. Self-sterile hermaphrodites were still able to mate with wild-type males, though, because egg production was unaffected. Male worms treated with auxin as larvae regained their virility after auxin withdrawal in adulthood, demonstrating that the system is reversible. The authors also compared their system to the common FUdR system; the new AID system resulted in longer lifespans, demonstrating that it’s a less toxic approach.
This new system, while an improvement over previous methods, is not without its drawbacks. Worms with degron-tagged spe-44 that were not treated with auxin still showed a detectable, though statistically insignificant, decrease in fertility, likely because the function of spe-44 was affected by the degron tag. Still, the AID system is a big advance over chemically toxic methods and is less labor-intensive than separating out adult worms by hand, leaving researchers more flexibility in designing assays to study longevity and mating.
Auxin-Mediated Sterility Induction System for Longevity and Mating Studies in Caenorhabditis elegans